Journal article
Noncanonical Transmission of a Measles Virus Vaccine Strain from Neurons to Astrocytes
MBIO, v 12(2), e00288-21
Mar 2021
PMID: 33758092
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Viruses, including members of the herpes-, entero-, and morbillivirus families, are the most common cause of infectious encephalitis in mammals worldwide. During most instances of acute viral encephalitis, neurons are typically the initial cell type that is infected. However, as replication and spread ensue, other parenchymal cells can become viral targets, especially in chronic infections. Consequently, to ascertain how neurotropic viruses trigger neuropathology, it is crucial to identify which central nervous system (CNS) cell populations are susceptible and permissive throughout the course of infection, and to define how viruses spread between distinct cell types. Using a measles virus (MV) transgenic mouse model that expresses human CD46 (hCD46), the MV vaccine strain receptor, under the control of a neuron-specific enolase promoter (NSE-hCD461 mice), a novel mode of viral spread between neurons and astrocytes was identified. Although hCD46 is required for initial neuronal infection, it is dispensable for heterotypic spread to astrocytes, which instead depends on glutamate transporters and direct neuron-astrocyte contact. Moreover, in the presence of RNase A, astrocyte infection is reduced, suggesting that nonenveloped ribonucleoproteins (RNP) may cross the neuron-astrocyte synaptic cleft. The characterization of this novel mode of intercellular transport offers insights into the unique interaction of neurons and glia and may reveal therapeutic targets to mitigate the life-threatening consequences of measles encephalitis. IMPORTANCE Viruses are the most important cause of infectious encephalitis in mammals worldwide; several thousand people, primarily the very young and the elderly, are impacted annually, and few therapies are reliably successful once neuroinvasion has occurred. To understand how viruses contribute to neuropathology, and to develop tools to prevent or ameliorate such infections, it is crucial to define if and how viruses disseminate among the different cell populations within the highly complex central nervous system. This study defines a noncanonical mode of viral transmission between neurons and astrocytes within the brain.
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Details
- Title
- Noncanonical Transmission of a Measles Virus Vaccine Strain from Neurons to Astrocytes
- Publication Details
- MBIO, v 12(2), e00288-21
- Publisher
- AMER SOC MICROBIOLOGY; WASHINGTON
- Grant note
- K.C.K.P. is a CabeauxJacobs Fellow of the King Baudouin Foundation, funded by the Belgian American Educational Foundation (2019) . This research was supported by R21 NS099788 (G.F.R.) , a gift from the F. M. Kirby Foundation, and Cancer Center Support Grant 5P30CA006927-53.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000643634500009
- Scopus ID
- 2-s2.0-85102836906
- Other Identifier
- 991021860757804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Microbiology